Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform

PHKA1 encodes the alpha regulatory subunit of phosphorylase b kinase, a serine kinase that phosphorylates substrates including troponin I and may bind calmodulin (UniProt: P46020). The protein is predominantly associated with skeletal muscle metabolism and glycogen regulation. PHKA1 mutations cause glycogen storage disease 9D (GSD9D), a progressive metabolic disorder featuring distal muscle weakness, exercise intolerance, and myoglobinuria (UniProt: P46020).

In Alzheimer's disease, PHKA1 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.5675 (Chaparral AD proteomics). This elevation was detected in a TMT-labeled proteomic study across four subcellular fractions (P2, P3, S2, S3) from human post-mortem samples. The functional significance of increased PHKA1 in AD pathology remains to be established.