PHYKPL (5-phosphohydroxy-L-lysine phospho-lyase) is a mitochondrial matrix enzyme that catalyzes the pyridoxal-phosphate-dependent breakdown of 5-phosphohydroxy-L-lysine into ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde. This lysine metabolism enzyme participates in amino acid catabolism through protein-binding interactions within the mitochondrion. PHYKPL has emerged as a metabolism-related biomarker in multiple disease contexts. In rheumatoid arthritis-associated interstitial lung disease (RA-ILD), PHYKPL expression is significantly upregulated in circulating monocytes alongside other genes regulating inflammation and fibrosis 1. The gene was identified as part of a nine-gene prognostic signature in osteosarcoma, where metabolism-related PHYKPL expression correlates with patient prognosis and survival outcomes 2. Additionally, PHYKPL was selected as one of ten aging marker genes in a transcriptome-based aging clock that detects accelerated aging in individuals with bacterial or viral infections, suggesting its role in aging and infection-related pathophysiology 3. In systemic sclerosis, PHYKPL exhibits altered intron retention patterns in skin tissue and TGF-β-stimulated fibroblasts, potentially contributing to abnormal fibrosis pathways 4. While the primary metabolic function of PHYKPL remains amino acid catabolism, its dysregulation appears associated with fibrotic diseases, malignancy, and aging acceleration, indicating broader pathophysiological relevance beyond classical phosphohydroxylysinuria.