Aspartyl/asparaginyl beta-hydroxylase

Aspartyl/asparaginyl beta-hydroxylase (ASPH) is a calcium-sensing protein that catalyzes hydroxylation of aspartate or asparagine residues within epidermal growth factor-like domains of various substrates (UniProt: Q12797). The enzyme functions as a structural component of endoplasmic reticulum–plasma membrane junctions and modulates calcium-release-activated calcium channel activity in immune cells. ASPH is a 758-amino-acid membrane-bound protein expressed in human tissues.

UniProt documents a monogenic association with facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs (FDLAB; MIM 601552), highlighting the protein's importance in connective tissue and ocular development. The molecular function in EGF-domain modification suggests roles in cell signaling and structural protein maturation across multiple tissues.

In Alzheimer's disease, ASPH is upregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics: mean log₂FC = 0.45, detected across 2 of 4 subcellular fractions in TMT-labeled quantitative proteomics). This modest elevation may reflect altered calcium homeostasis or ER stress responses characteristic of the AD pathological state, though functional implications remain to be determined.