CRISPLD1 (cysteine-rich secretory protein LCCL domain containing 1) is a member of the CAP superfamily of secreted proteins 1. The protein is primarily involved in developmental processes, particularly craniofacial morphogenesis, with expression documented in developing murine craniofacial tissues 2. Mechanistically, CRISPLD1 appears to function through ion channel regulation, with structural homology to ion channel regulatory toxins suggesting roles in calcium cycling 3. The protein contains elevated cysteine residues compared to similarly-sized proteins 2, and the CAP superfamily broadly participates in extracellular matrix regulation and branching morphogenesis 1. CRISPLD1 has documented disease relevance in multiple conditions. In nonsyndromic cleft lip and palate (NSCLP), CRISPLD1 interacts with CRISPLD2 and folate pathway genes to influence disease susceptibility 2. In heart failure, CRISPLD1 is upregulated during the transition to failure, and loss-of-function studies show dysregulated calcium handling and altered expression of hypertrophic and apoptotic pathways 3. Additionally, CRISPLD1 exhibits differential DNA methylation in infertile male patients 4, appears as a progesterone receptor coexpressed gene in endometrial cancer progression 5, and is differentially expressed in irreversible pulpitis 6. These findings suggest CRISPLD1 represents a novel therapeutic target in developmental disorders, heart failure, and potentially cancer and reproductive pathologies.