PHC1 (polyhomeotic homolog 1) is a component of the Polycomb Repressive Complex 1 (PRC1) that plays crucial roles in chr12 remodeling and transcriptional regulation. The protein maintains transcriptional repression through histone H2A monoubiquitination at lysine 119, which renders chr12 heritably silenced 1. Beyond its canonical repressive function, PHC1 exhibits dual regulatory capabilities by activating Nanog transcription in pluripotent cells through stabilizing genome-wide chr12 interactions at the Nanog locus, independent of PRC1 2. PHC1 also controls cellular levels of Geminin expression, which is essential for proper cell cycle regulation 1. Disease-wise, PHC1 mutations are associated with primary microcephaly 11 (MCPH11), an autosomal recessive neurodevelopmental disorder characterized by reduced brain size at birth 134. Patients with PHC1 mutations exhibit decreased protein expression, elevated Geminin levels, defective histone H2A ubiquitination, and aberrant DNA damage repair 1. The gene is located on chromosome 12 and consists of 15 exons spanning approximately 26 kb 5. These findings highlight PHC1's critical role in chr12 organization, cell cycle control, and neurodevelopment, with mutations leading to microcephaly through disrupted chr12 remodeling mechanisms.