Autoimmune and autoinflammatory diseases significantly impair survival and quality of life, affecting around 10% of the global population. Both the innate and adaptive immune systems' aberrant activation is a feature of several disease types. Interestingly, it has also been demonstrated that autoinflammatory and autoimmune diseases are genetically linked to the endoplasmic reticulum aminopeptidase 1 (ERAP1) protein. This protein is well known for its aminopeptidase function as a "molecular ruler," trimming peptides prior to their loading onto MHC-I molecules for antigen presentation in the ER. It has been discovered that this complex protein performs a wide range of roles that influence the innate and adaptive immune responses. We present a summary of these findings in this review in an effort to pinpoint potential ERAP1- dependent pathways that underlie the etiology of several ERAP1-related illnesses.