ICA1 (islet cell autoantigen 1) is a neuroendocrine protein with roles in neurotransmitter secretion and protein trafficking. The protein exhibits tissue-specific expression, with high levels in pancreatic islets, brain, and testis 1. Subcellularly, ICA1 localizes to the endoplasmic reticulum, Golgi complex, and secretory vesicles, suggesting involvement in protein processing and transport 1. ICA1 expression is regulated through alternative core promoters in a tissue-specific manner, with distinct regulatory elements in islet versus neuronal cells 2. In Alzheimer's disease pathology, ICA1 modulates amyloid precursor protein (APP) processing by regulating the PICK1-PKCα signaling pathway, promoting non-amyloid pathways and reducing pathogenic APP cleavage 3. ICA1 is implicated in type 1 diabetes (T1D) autoimmunity; polymorphisms in the ICA1 promoter increase binding of the autoimmune regulator (AIRE), reducing thymic ICA1 expression and potentially compromising self-tolerance 4. DNA methylation patterns of ICA1 differ between T1D patients and healthy individuals, with hypermethylation associated with altered expression in affected individuals 5. Additionally, ICA1 genetic variants show suggestive associations with germinal centre formation in primary Sjögren's syndrome, indicating broader autoimmune disease relevance 6.