HYI (hydroxypyruvate isomerase) catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate, participating in glyoxylate metabolic processes 1. The protein functions through protein-protein binding interactions, notably interacting with protein P311 via α-helical domains in fibroblast contexts 2. Beyond its canonical enzymatic role, HYI has emerged as a significant disease biomarker. Mendelian randomization analysis identified HYI as a brain and cerebrospinal fluid protein with causal genetic connections to attention deficit hyperactivity disorder (ADHD) risk 3. In colorectal carcinoma, HYI expression was significantly downregulated in cancer tissues compared to paracancerous tissue and identified among key differentially expressed proteins in a multi-omics diagnostic classifier model 1. HYI was also detected as a core differentially expressed protein in hepatocellular carcinoma risk prediction for HIV/HBV co-infected patients 4. Clinically, anti-HYI autoantibodies were discovered as novel biomarkers with diagnostic potential for early-stage breast cancer, showing 20.41-28.57% individual sensitivity and >90% specificity; inclusion in a 5-antibody panel improved sensitivity to 38.78% 5. Additionally, HYI transcription is affected by noncoding somatic mutations in cancers, with effects reproducible across multiple cancer cell lines 6. These findings suggest HYI's potential value in cancer diagnostics and neuropsychiatric disease pathogenesis.