HDGF like 1 (HDGFL1) is a nuclear protein involved in chr6 remodeling located on chromosome 6. While its precise molecular mechanism remains incompletely characterized, HDGFL1 has emerged as a genetic risk factor across multiple complex traits and diseases. In cardiac aging, HDGFL1 variants were identified as one of 24 loci associated with cardiac age acceleration, a heritable trait (h²g 26.6%) linked to unfavorable cardiac geometry and dysfunction 1. The gene also shows associations with cardiovascular disease risk; genome-wide cross-trait analysis revealed HDGFL1 as a novel shared genetic locus between attention-deficit/hyperactivity disorder and multiple cardiovascular diseases including heart failure and myocardial infarction 2. In cancer contexts, autoantibodies against HDGFL1 were identified in esophageal squamous cell carcinoma patients and incorporated into diagnostic prediction models 3, while HDGFL1 was identified as a prognostic immune-related gene in hepatocellular carcinoma 4. Additionally, HDGFL1 variants associate with serum iron metabolism markers 5 and cognitive function in elderly Japanese populations, with functional annotation suggesting involvement in chr6 structure regulation and iron metabolism pathways 6. These diverse associations suggest HDGFL1 may influence fundamental cellular processes relevant to aging, cardiac homeostasis, and disease susceptibility.