C1RL (complement C1r subcomponent like) is a serine-type endopeptidase with emerging roles in disease pathogenesis beyond its canonical complement function. While the UniProt database indicates C1RL mediates proteolytic cleavage of haptoglobin in the endoplasmic reticulum, recent evidence reveals broader disease associations. C1RL expression is upregulated in glioblastoma, particularly mesenchymal and primary subtypes, correlating with reduced tumor purity, increased M2 macrophage infiltration, and unfavorable survival outcomes 1. In melanoma, C1RL emerges as a key serum biomarker differentiating anti-PD-1 therapy responders from non-responders 2. Genetic studies identify C1RL as a genetically supported druggable target for brain aging 3, with its long non-coding RNA transcript C1RL-AS1 showing disease relevance through m6A-mediated regulation in lung cancer 4 and association with ocular Behçet's disease susceptibility 5. C1RL-AS1 additionally aggravates influenza A virus pneumonia through a miR-16-5p/LAMP3 regulatory axis 6, while biallelic loss-of-function variants associate with autosomal recessive Parkinson's disease 7. These findings suggest C1RL functions as an immunoregulatory protein with pleiotropic effects across neurological, inflammatory, and neoplastic diseases, representing a promising therapeutic target.