Serine protease autotransporters of Enterobacteriaceae (SPATE) constitute a superfamily of virulence factors, resembling the trypsin‐like superfamily of serine proteases. SPATEs accomplish multiple functions associated to disease development of their hosts, which could be the consequence of SPATE cleavage of host cell components. SPATEs have been divided into class‐1 and class‐2 based on structural differences and biological effects, including similar substrate specificity, cytotoxic effects on cultured cells, and enterotoxin activity on intestinal tissues for class‐1 SPATEs, whereas most class‐2 SPATEs exhibit a lectin‐like activity with a predilection to degrade a variety of mucins, including leukocyte surface O‐glycoproteins and soluble host proteins, resulting in mucosal colonization and immune modulation. In this review, the structure of class‐1 and class‐2 are analyzed, making emphasis on their putative functional subdomains as well as a description of their function is provided, including prototypical mechanism of action.