Recombinant Human ALS2CL Protein

Recombinant human ALS2 C-terminal like protein (ALS2CL) is a conserved eukaryotic protein sharing significant homology with the C-terminal region of alsin, encoded by the ALS2 gene. Alsin mutations are linked to autosomal recessive forms of juvenile amyotrophic lateral sclerosis (ALS2), hereditary spastic paraplegia (HSP), and infantile-onset ascending spastic paralysis. ALS2CL contains a VPS9 domain, a hallmark feature of guanine nucleotide exchange factors (GEFs) for Rab5 GTPases, which regulates endosomal trafficking and membrane dynamics. While alsin primarily localizes to early endosomes and modulates Rab5-mediated pathways critical for neuronal maintenance, ALS2CL's precise cellular role remains less defined, though it is speculated to influence similar Rab5-dependent processes or alternative signaling cascades.

Studies suggest ALS2CL may compensate for ALS2 loss in cellular models, potentially mitigating neurotoxicity caused by aberrant endolysosomal function. However, its exact physiological relevance in vivo is unclear, as ALS2CL knockout mice lack overt neurological phenotypes. Intriguingly, ALS2CL interacts with proteins involved in vesicle transport and cytoskeletal organization, implicating it in broader cellular homeostasis beyond Rab5 activation. Its recombinant form is commonly utilized in structural studies and functional assays to dissect molecular interactions, particularly in neurodegenerative disease contexts. Despite progress, questions persist regarding its tissue-specific roles, post-translational modifications, and potential contribution to overlapping pathologies like ALS or HSP. Ongoing research aims to clarify its therapeutic potential as a modifier of endosomal dysfunction in motor neuron diseases.