PPP2R3C encodes the B''gamma regulatory subunit of protein phosphatase 2A (PP2A), functioning primarily as a centrosomal protein that regulates phosphorylation networks critical for development and cellular homeostasis 1. The protein localizes to the distal centriole where it forms a functional partnership with centriolar proteins CEP350 and FOP, counteracting MAP3K1 kinase activity to maintain balanced centrosome function 1. PPP2R3C negatively regulates P-glycoprotein (ABCB1) expression and function through dephosphorylation, affecting multidrug resistance mechanisms 2. Additionally, it serves as a positive regulator of Hedgehog signaling by interacting with Gli proteins and antagonizing MEKK1 kinase activity 3. Clinically, homozygous PPP2R3C variants cause myoectodermal gonadal dysgenesis syndrome (MEGD), characterized by complete gonadal dysgenesis in both 46,XY and 46,XX individuals, along with distinctive facial features and multiple organ system abnormalities 456. Heterozygous variants are associated with impaired spermatogenesis and male infertility 4. The protein's essential role is highlighted by embryonic lethality in homozygous knockout mice 6. PPP2R3C has also been implicated in cancer prognosis and autoimmune conditions 78.