PPP1R21 encodes a regulatory subunit that serves as a central component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary), functioning as a binding hub that connects all five complex subunits and mediates binding to mRNA and early endosomes via RAB5A 1. The FERRY complex directly interacts with mRNAs and functions as a RAB5A effector involved in localizing and distributing specific mRNAs through endosomal transport, recruiting mRNAs and ribosomes to early endosomes 2. PPP1R21 localizes to early endosomes and plays a role in the endosomal sorting process or endosome maturation pathway 3. Biallelic loss-of-function variants in PPP1R21 cause a neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, characterized by global developmental delay, coarse facial features, and brain imaging abnormalities including delayed myelination and ventricular changes 34. Patient fibroblasts exhibit delayed transferrin clearance, indicating impaired endocytic function 3. The disorder represents part of an emerging disease class affecting FERRY complex components, suggesting shared pathogenic mechanisms involving mRNA transport and endosomal function 2. Additionally, PPP1R21 variants may influence stroke recovery outcomes, potentially through effects on brain plasticity mechanisms 5.