Mutations in the ALS2 gene result in a number of juvenile recessive motor neuron diseases (MNDs), including juvenile primary lateral sclerosis (JPLS), a recessive form of amyotrophic lateral sclerosis (ALS2), infantile onset ascending hereditary spastic paralysis (IAHSP) and a form of complicated hereditary spastic paraplegia (cHSP). The ALS2 gene encodes the Alsin protein. Alsin acts as a guanine nucleotide exchange factor for Rab5, a modulator of the endocytic pathway. Alsin is a cytosolic protein, which is associated with small, punctate membrane structures. Therefore Alsin may mediate membrane transport events, potentially linking endocytic processes and actin cytoskeleton remodeling. The ALS2 C-terminal like protein (ALS2CL) also modulates Rab5 activity.
