FAM53C is a cytoplasmic anchoring protein that functions as a critical negative regulator of cell cycle progression through direct inhibition of the kinase DYRK1A 1. FAM53C binds to the catalytic domain of DYRK1A, suppressing both its autophosphorylation activity and kinase activity toward substrates like tau protein 2. Mechanistically, FAM53C-DYRK1A interaction induces cytoplasmic relocalization of DYRK1A from the nucleus, preventing DYRK1A-dependent nuclear accumulation of binding partner DCAF7/WDR68 2. At the cellular level, FAM53C acts upstream of the Cyclin D-CDK4/6-RB axis to regulate G1/S cell cycle transition, with FAM53C knockdown causing G1 arrest that is rescued by DYRK1A kinase inhibition 1. FAM53C knockout in human cortical organoids results in increased cell cycle arrest and growth defects, while Fam53C knockout mice exhibit body growth and behavioral abnormalities 1. Given that DYRK1A dysregulation contributes to Down syndrome and neurodevelopmental disorders, FAM53C represents a potential therapeutic target for developmental and oncological diseases 1. Additionally, FAM53C shows inverse expression correlation with obesity-associated miRNAs in blood, suggesting potential roles in metabolic regulation 3.