Over the course of the series, and with the significant support of several friends and role models who also struggle with LGBT+ issues, Shuichi comes to terms with her identity as a transgender girl. I'll use female pronouns to reflect this.
Shuichi certainly struggles with being accepted for her preferences, starting with her home life and her sister, Maho, who outspokenly opposes her transition and views it as a sickness. However, Shuichi isn't framed by the show as a joke or as an inherent outcast-- a fact that is almost surprising considering the strict norms of Japanese society.
Rather than being singled out as the only person facing problems of acceptable identity, Shuichi is surrounded by many supporting characters who don't fit the social mold either.
One close friend, Yoshino Takatsuki, is a transgender boy. Yoshino and Shuichi have known each other through elementary school, and continue to experience the growing pains of getting older together. He is the clearest parallel and complement to Shuichi's situation, and somewhat of a complicated love interest.
Another friend, Makoto Ariga, is introduced as a boy who is questioning his sexuality. Makoto experiments with cross-dressing with Shuichi and ultimately comes to the conclusion that she is also a transgender girl.
A mentor figure appears in the form of Yuki Yoshida, an adult transsexual woman. She lives with her boyfriend after being rejected by her family, but has found a successful career running a gay bar. With her relevant life experience, she is able to offer advice to Shuichi and Yoshino.
Not everyone is friendly and compatible at first brush. Anna Suehiro, who plays an important role as Shuichi's first real relationship, is a girl who initially teases him for his cross-dressing, but the two soon develop genuine interest in each other. She comes to accept Shuichi as a person rather than necessarily as a boy or girl, gets to understand her feelings, and goes on a date with her while in feminine clothes, not minding if she is seen as a lesbian. Their relationship may not work out in the end, but it leaves an impact on them both.
The series deals with the double standards of gender presentation: Chizuru and Yoshino each come to school in a male uniform without much consequence, but many people -- including Yoshino herself -- at some point criticize Shuichi for wanting to wear a female uniform in public. It also touches upon the background radiation that contributes to the gendered society: Constant references appear in casual conversations as to what "girls should do" and what "boys should do." Even the title of the first episode, referencing a common nursery rhyme, asks the question, "What are little girls made of?"
Utilizing the character-centered nature of the slice-of-life genre to its fullest, despite the slow plot, relationships and feelings take center stage. To create the context, the majority of the plotline revolves around Shuichi's middle-school class preparing to produce and perform a "gender-bender" play, one which purposely casts males in female roles and vice versa. Somewhat fittingly, the play they choose to present is based on Romeo and Juliet. Shuichi helps write the script, re-envisioning the story to reflect the themes of the actors' own gender insecurities. As many characters are being given their first major chance to publicly play a different gendered role, this setting offers a significant frame for their exploration.
Many of the characters are able to "pass" attractively as both genders whose roles they explore, due to a sense of natural physical androgyny. Natural androgyny is often used as a convenient handwave to justify gender-bending characters, but in this show they are also shown to run into physical challenges when the effects of puberty hit. Yoshino becomes anxious over developing breasts and the pressure to wear a bra, while Shuichi's deeper voice and changing body begins to makes her less comfortable in her femininity... but, once again, they have support to encourage them through it.
Often, there will be just one gender-bending character in a fictional world, who stands out from the rest specifically because of their non-conformance. This is neither inherently good nor inherently bad, always depending upon the context and the respect given to the situation. Of course, one cannot call the opposite inherently bad either. It may be criticized as unrealistic to have such a high of LGBT+ representation in a single set of characters, but I believe that the spectrum of feelings explored is more common than may be expected, and that people with similar issues and mindsets do tend to find each other. Regardless, any argument about over-representation ruining realism seems a bit mean-spirited, since it is so important both inside and outside of the fourth wall for people to know that they are not alone.
This review was suggested by Tumblr user toyherb, whom I thank for introducing me to such a beautiful show!