Alsin Rho guanine nucleotide exchange factor ALS2 (ALS2)

Alsin Rho guanine nucleotide exchange factor ALS2 is a multidomain protein encoded by the ALS2 gene that serves as a guanine nucleotide exchange factor (GEF) for small GTPases, primarily Rab5 and Rac1. Alsin is highly expressed in the central nervous system, especially in motor neurons of the brain and spinal cord, where it regulates endosomal trafficking, cytoskeletal remodeling, and neuronal outgrowth. Disruption of ALS2 function through gene mutation causes inherited neurodegenerative syndromes including juvenile-onset amyotrophic lateral sclerosis (ALS2), infantile-onset ascending hereditary spastic paralysis, and juvenile primary lateral sclerosis. These disorders manifest as progressive muscle weakness and degeneration of upper motor neurons, thought to arise from defects in endocytic vesicle processing, receptor recycling, and cytoskeletal maintenance, for which alsin is essential. There are currently no known direct pharmacological therapies targeting ALS2, and its major relevance is in neurogenetic diagnostics and disease pathogenesis.

Other names

AlsinALS2CR6KIAA1563Amyotrophic lateral sclerosis 2 proteinIAHSPALSJPLSJAmyotrophic lateral sclerosis 2 (juvenile)ALS2_HUMAN