ICA1L (islet cell autoantigen 1 like) is a BAR-domain protein involved in membrane trafficking and vesicle dynamics. Functionally, ICA1L regulates secretion and membrane curvature through its interaction with PICK1, forming BAR-domain complexes essential for proper vesicle trafficking 1. In spermiogenesis, ICA1L is the major PICK1 binding partner in testes; ICA1L knockout mice show abnormal acrosome, nucleus, and mitochondrial formation, reducing sperm mobility and fertility 1. Disease relevance is substantial. ICA1L expression associates causally with multiple neurological conditions: Alzheimer's disease risk reduction through brain protein abundance 23, ADHD protection 4, and intracerebral hemorrhage risk 5. Genome-wide association studies identify ICA1L in loci associated with lacunar stroke 6 and migraine, where it likely modulates neuronal signaling and inflammatory responses 7. Clinically, ICA1L represents a potential therapeutic target for neurodegenerative diseases and stroke, though some studies caution against prioritizing it as a drug target due to potential side effects 3. ICA1L is predominantly expressed in excitatory-inhibitory neurons and glutamatergic neurons 42, suggesting its role in cerebral pathology may be neuron-specific. The protein also participates in myofibroma pathogenesis through gene fusion events 8.