The endoplasmic reticulum quality control (ERQC) system is a core mechanism for maintaining cellular homeostasis, which primarily mediates the degradation of misfolded proteins in the endoplasmic reticulum (ER) through the ER-associated degradation (ERAD) and ER autophagy (ER-phagy) pathways. Tripartite motif 13 (TRIM13) is a protein located on the ER membrane, which plays a critical role in ERAD via its E3 ubiquitin ligase activity. TRIM13 also acts as a non-classical ER-phagy receptor to mediate the occurrence of ER-phagy. TRIM13 has recently received extensive attention in the field of ERQC. Here we review the structure and function of TRIM13 and the mechanisms by which it contributes to ERQC, and summarize its abnormal expression and regulatory role in diseases, with the aim of providing new strategies for the treatment of related diseases.