Platelet-activating factor acetylhydrolase IB subunit beta

PAFAH1B1 encodes the regulatory beta subunit of cytosolic platelet-activating factor acetylhydrolase type I (PAF-AH), an enzyme that inactivates platelet-activating factor by hydrolyzing its acetyl group at the sn-2 position (UniProt: P43034). Beyond lipid metabolism, PAFAH1B1 functions in neuronal migration and cytoskeletal dynamics by regulating dynein-mediated microtubule processes, including nuclear translocation during corticogenesis and maintenance of Golgi integrity. It may also modulate Reelin signaling through interaction with VLDLR.

In the nervous system, PAFAH1B1 is essential for brain development, specifically neuronal precursor proliferation and migration from the ventricular zone. Mutations cause classical lissencephaly (LIS1), subcortical band heterotopia, and Miller-Dieker lissencephaly syndrome—severe neuronal migration disorders characterized by cortical disorganization (UniProt: P43034).

In Alzheimer's disease, PAFAH1B1 shows ambiguous regulation across subcellular fractions from human post-mortem AD brain proteomics, with a mean log2 fold-change of −0.093 relative to age-matched controls (Chaparral AD proteomics). The modest magnitude and directional inconsistency across fractions suggest minimal or context-dependent perturbation in AD pathology.