Crispld1, short for cysteine-rich secretory protein LCCL domain containing 1, belongs to the CAP superfamily. Its functions may be related to ion channel regulation, as its homology to ion channel regulatory toxins suggests a role in Ca2+ cycling [2]. It is expressed in various tissues such as the nasal glands, cartilages during murine nasal development [5], and is also associated with the chondrocyte stress response in cartilage degradation [6].

In gastric cancer, knockdown of Crispld1 reduced cell proliferation, invasion, and migration. It decreased intracellular calcium levels and inhibited the PI3K-AKT signaling pathway, indicating that Crispld1 promotes gastric cancer progression by mediating intracellular calcium levels and activating this pathway [1].

In the transition to human heart failure, Crispld1 is upregulated. Nuclease technology-mediated loss-of-function in human-induced pluripotent stem cell-derived cardiomyocytes led to dysregulated Ca2+ handling, and its downregulation affected prohypertrophic, proapoptotic and Ca2+-signaling pathways, suggesting its contribution to adverse remodeling [2].

In coronary artery disease patients, the rs12115090 A>C polymorphism of Crispld1 increased the antiplatelet potency of clopidogrel, with carriers of the C allele having a reduced risk of high on-treatment platelet reactivity [3].

For nonsyndromic cleft lip and palate, though there was little evidence for Crispld1 variation alone playing a role, interactions were detected between Crispld1/2 SNPs and folate pathway genes [4].

In summary, Crispld1 plays diverse roles in different biological processes and diseases. Model-based research, such as knockdown in gastric cancer cells and Nuclease technology-mediated loss-of-function in cardiomyocytes, has revealed its importance in processes like cancer cell progression, heart failure transition, anti-platelet response, and potentially in the development of cleft lip and palate. These findings highlight its potential as a therapeutic target in related diseases.