CRISPLD2 (cysteine rich secretory protein LCCL domain containing 2) is a secreted extracellular matrix protein that functions as an anti-inflammatory mediator and regulator of tissue homeostasis. The protein is glucocorticoid-responsive and plays a critical role in suppressing proinflammatory cytokines including IL-6, IL-8, and CCL2 in airway smooth muscle cells and lung fibroblasts 12. CRISPLD2 operates through multiple molecular mechanisms, including modulation of the YAP/TEAD1 transcriptional complex in hepatocellular carcinoma 3 and regulation of the miR-548I-IL17A axis to prevent oxidative stress-induced ferroptosis in intervertebral disc degeneration 4. The protein demonstrates significant clinical relevance across multiple diseases. Genetic polymorphisms in CRISPLD2 are associated with increased risk of nonsyndromic cleft lip/palate 5 and corticosteroid resistance in asthma patients 1. CRISPLD2 expression is elevated in senescent fibroblasts that promote bladder cancer progression 6 and serves as a biomarker in osteoarthritis 7. Therapeutically, CRISPLD2 overexpression shows promise for treating intervertebral disc degeneration by preventing ferroptosis 4, while its modulation may offer targets for cancer therapy 3.