Platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1)

Platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1), commonly known as LIS1, encodes a non-catalytic regulatory subunit of the platelet-activating factor acetylhydrolase IB enzyme complex[1][3][4]. This protein is essential for proper neuronal migration in brain development by regulating cytoplasmic dynein, which powers intracellular transport along microtubules. LIS1’s interactions with microtubule-associated proteins direct cytoskeletal organization, spindle orientation, and cell division crucial to neurogenesis. Mutations or deletions in PAFAH1B1 cause lissencephaly and Miller–Dieker syndrome, characterized by brain malformations, severe intellectual disability, and seizures. Beyond the nervous system, abnormal PAFAH1B1 activity can influence cancer cell motility, vascular development, and stem cell dynamics. There is currently no direct therapeutic agent targeting PAFAH1B1; genetic testing for its mutations serves as a diagnostic biomarker in lissencephaly-spectrum disorders[3][4].

Other names

LIS1LIS-1MDCRMDSPAFAHAPAF-AH 45 kDa subunitPAFAH alphaPAF-AH alphaLissencephaly-1 proteinNudFplatelet-activating factor acetylhydrolase IB subunit betaplatelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45 kDa)subcortical band heterotopia protein

Potential small-molecule or genetic modulation of the LIS1-dynein interaction to alter neuronal migration or cell division[4]. Disruption by pathogenic proteins (e.g., viral proteins) that bind and inactivate LIS1[4].