Abstract: ApeC-containing proteins (ACPs) were first identified in 2014. Subsequent studies have revealed that ACPs represent a novel class of pattern recognition molecules widely distributed in aquatic invertebrates and some bacteria. ACPs contain a characteristic ApeC domain, which adopts a conserved three β-sheet fold and can combine with various partner domains to form diverse protein architectures. This review summarizes the discovery, classification, origin, evolution, and functional studies of ACPs, with a focus on their roles in amphioxus, echinoderms, cnidarians, mollusks, parasitic flatworms, and bacteria, including pathogen recognition, mucosal defense, cell adhesion, developmental regulation, and parasitic adaptation. We discuss the evolutionary trajectory of ACPs from ancestral lectin-like molecules toward immune receptors. This review aims to provide a reference for future studies on the structure- function relationships of the ApeC domain and for subsequent basic and applied research.