Glycogen Phosphorylase, Muscle Form (PYGM)

Glycogen phosphorylase, muscle form is an allosteric enzyme encoded by PYGM that catalyzes the rate-limiting step in glycogen catabolism, cleaving glycogen phosphorolytically to generate glucose-1-phosphate and thereby maintaining cellular and organismal glucose homeostasis (UniProt: P11217).

The protein is predominantly expressed in skeletal muscle tissue. Mutations in PYGM cause glycogen storage disease 5 (GSD5), a metabolic myopathy characterized by exercise intolerance, muscle cramps, weakness, and recurrent myoglobinuria (UniProt: P11217). This underscores the critical role of glycogen breakdown in muscle energy metabolism.

PYGM is upregulated in Alzheimer's disease brain tissue, with a mean log2 fold-change of +0.7757 in post-mortem AD brain relative to age-matched controls in human TMT-labeled proteomics across four subcellular fractions (Chaparral AD proteomics). The upregulation may reflect altered glucose metabolism or metabolic stress responses in the AD brain, though the functional significance of this change remains to be clarified.