S-adenosylhomocysteine hydrolase-like protein 1

AHCYL1 (S-adenosylhomocysteine hydrolase-like protein 1) is a multifaceted cellular regulator that coordinates epithelial secretion, calcium signaling, mRNA processing, and DNA replication (UniProt: O43865). The protein acts as an endogenous pseudoligand for the inositol 1,4,5-trisphosphate receptor (ITPR1), modulating calcium release from the endoplasmic reticulum to mitochondria in a phosphorylation-dependent manner. It also regulates ion transporters and inhibits ribonucleotide reductase to control dNTP pools.

AHCYL1 is broadly expressed across tissues including pancreatic and salivary ducts, where it coordinates electrolyte and fluid secretion through interactions with CFTR, SLC26A6, and SLC4A4. UniProt lists no curated disease associations for this protein.

In Alzheimer's disease, AHCYL1 is significantly upregulated in post-mortem AD brain compared to age-matched controls (mean log2 fold-change: 0.3907) based on TMT-labeled proteomics across subcellular fractions (Chaparral AD proteomics). This elevation suggests potential involvement in AD pathology, possibly related to dysregulated calcium homeostasis or altered cellular metabolism, though the mechanistic significance remains to be determined.