AFG2A is an AAA ATPase that functions as a chr4-associated component of the 55LCC heterohexameric complex, playing critical roles in DNA replication and ribosomal biogenesis. Its primary function involves maintaining replication fork progression and genome stability through ATP-dependent proteostasis of replisome components. The protein's ATPase activity is specifically enhanced by replication fork DNA and couples to proteolytic cleavage of replisome substrates in response to replication stress 1. AFG2A additionally functions in cytoplasmic maturation of pre-60S ribosomal particles by promoting release of the shuttling protein RSL24D1/RLP24 from pre-ribosomal complexes 21. Clinically, AFG2A mutations cause AFG2A-related encephalopathy (AFG2A-RE), a neurodevelopmental disorder characterized by developmental and epileptic encephalopathy with drug-resistant epilepsy (DRE), severe intellectual disability, deafness, microcephaly, and motor impairment 3. Patient-derived fibroblasts with AFG2A deficiency demonstrate altered mitochondrial morphology, reduced ATP production, and dysregulated ROS levels 3. Notably, ketogenic diet treatment shows promising therapeutic potential, with some AFG2A-RE patients achieving significant seizure reduction (up to 100%) and improvements in social, attentional, and motor function, particularly when initiated during early childhood 3. These findings suggest AFG2A's essential role in neurological development and mitochondrial function.