PAGR1 (PAXIP1 associated glutamate rich protein 1) functions as a multifaceted chr16 regulatory protein with critical roles in development, gene expression, and genome stability. The protein forms a heterodimeric complex with PAXIP1 that regulates cohesin chr16 association independently of DNA replication, promoting global cohesin occupancy at active gene promoters and enhancers 1. This PAXIP1-PAGR1 complex requires a conserved FDF motif in PAGR1 for cohesin regulation and co-localizes with cohesin across multiple genomic loci 1. PAGR1 functions as a tumor suppressor in lung cancer, forming a STAG2-PAXIP1/PAGR1 axis that suppresses tumorigenesis through effects on gene expression, chr16 accessibility, and 3D genome conformation 2. During embryonic development, PAGR1 is essential for extraembryonic tissue formation, with mouse Pagr1a knockout embryos showing defective amnion and chorion development, reduced BMP2 expression, and developmental arrest at the four- to five-somite stage 3. Biallelic variants in PAGR1 cause a severe neurodevelopmental disorder characterized by microcephaly, developmental delay, and early lethality, with complete knockout being embryonic lethal in mice 4. The gene is also implicated in metabolic regulation and body mass index control 5.