Unconventional myosin-Va

MYO5A encodes unconventional myosin-Va, a processive actin-based motor protein that hydrolyzes ATP to generate force for transport along actin filaments. It plays a central role in melanosome transport and mediates vesicle transport to the plasma membrane. The protein may also participate in dendrite polarization processes (UniProt: Q9Y4I1).

MYO5A is widely expressed and mutations in this gene cause Griscelli syndrome 1 (GS1), a rare autosomal recessive disorder characterized by pigmentary dilution, intellectual disability, and hypotonia (UniProt: Q9Y4I1). The protein functions in multiple subcellular compartments relevant to membrane trafficking and cellular transport.

In Alzheimer's disease, MYO5A shows reduced expression in post-mortem brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein is consistently downregulated across examined subcellular fractions with a mean log2 fold-change of −0.34, suggesting diminished motor protein availability in AD pathology. This reduction may impair vesicular and organellar transport, contributing to cellular dysfunction in neurodegeneration.