APH1B is a stabilizing subunit of the gamma-secretase complex that catalyzes intramembrane cleavage of proteins including amyloid precursor protein (APP) and Notch receptors 1. The protein functions as a cofactor that promotes stable complex formation, though it is present in a minority of gamma-secretase complexes compared to APH1A 1. APH1B plays a crucial role in axonal guidance by working antagonistically with BACE1 to regulate growth cone collapse through proteolytic processing of CHL1 fragments in response to semaphorin 3A signaling 2. In disease contexts, APH1B shows significant genetic associations with Alzheimer's disease risk, with multiple genome-wide association studies identifying it as a risk gene 34. Dysregulated APH1B expression in peripheral blood correlates with brain atrophy and amyloid-β deposition in Alzheimer's disease patients 5. Additionally, specific variants in APH1B are strongly associated with tau-related pathology in brain tissue 6. The gene also demonstrates oncological relevance, as it maintains stemness in cervical cancer stem cells when regulated by HPV16 E7 7 and serves as a prognostic marker in ovarian cancer 8.