The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. From RefSeq]

The ALS2 gene belongs to a family of genes called ARHGEF (Rho guanine nucleotide exchange factors). The ALS2 gene is located on human chromosome 2q33.2, from region 202,273,521 to 202,353,982, and has 34 exons; the transcript length is 6,644 bps. The Alsin protein consists of 1657 amino acids and weighs 183634 Da. The expression of the gene is normally found in various tissues and cells, including neurons throughout the brain and spinal cord.

Researchers have identified at least eight mutations in the ALS2 gene in association with various forms of Amyotrophic Lateral Sclerosis (ALS). All the mutations lead to unstable protein which breaks down rapidly by the cell, or it will disable the protein function. Four of these mutations have been identified to cause juvenile primary lateral sclerosis. In affected members three deletion mutations have been identified in exons 3, 5 and 9. Patients carrying the 1-bp deletion in exon 3 had more severe phenotype than others.