PHYH (phytanoyl-CoA 2-hydroxylase) is a peroxisomal Fe(II) and 2-oxoglutarate-dependent oxygenase that catalyzes the critical first step of phytanic acid alpha-oxidation 1. The enzyme hydroxylates phytanoyl-CoA and various mono-branched 3-methylacyl-CoA esters with chain lengths ≥7 carbons, but lacks activity toward long-chain straight-chain acyl-CoAs or 2/4-methyl-branched variants 23. This selectivity enables metabolism of phytanic acid, an epimeric branched-chain fatty acid from chlorophyll that cannot undergo beta-oxidation, converting it to pristanic acid for subsequent degradation 1. Phytanoyl-CoA 2-hydroxylase mutations cause adult Refsum disease (ARD), a neurological disorder characterized by phytanic acid accumulation in plasma and tissues 14. The PHYH gene spans ~21 kb with nine exons; disease-causing mutations cluster around Fe(II)- and 2-oxoglutarate-binding sites and universally ablate enzymatic activity 41. Notably, Refsum disease shows genetic heterogeneity, as mutations in the peroxisomal targeting receptor PEX7 also cause the disease 5. Beyond lipid metabolism, PHYH expression may influence broader metabolic pathways. In renal cell carcinoma, PHYH expression correlates with survival outcomes and associates with PPAR signaling and pyruvate metabolism 6. Recent characterization of the PHYH c.678+5G>T variant identified in-frame exon skipping associated with attenuated Refsum disease phenotypes 7.