Isadora Oliveira, Isabela Ferreira, Lorena Sousa, João Alberghini-Dos-Santos, Felipe Cerni, Manuela Pucca
Crotamine is a low-molecular-weight cationic polypeptide isolated from Crotalus durissus terrificus snake venom, classified as a non-enzymatic toxin with distinctive structural and functional properties. This toxin also exhibits characteristics of a cell-penetrating peptide, owing to its ability to translocate across biological membranes in a largely non-specific manner and to deliver diverse molecular cargos into cells. Beyond its well-established internalization capacity, emerging evidence suggests that crotamine exerts immunomodulatory effects. In our mini review, we discuss current advances in understanding crotamine as a venom-derived immunomodulatory peptide, highlighting its structural similarities with host defense peptides, its interactions with immune cells, and its potential applications in immunotherapy and drug delivery.