Although the discovery that the ribosomal protein RPL26 as a predominant UFMylation substrate had shed insights into the role of UFM1 in maintaining ER homeostasis (Figure 1) [35,36,38], it also establishes the contribution of the UFM1 system to a variety of diseases arising from disturbance of ER homeostasis ranging from cardiac disease, gut inflammation, and cancer [64,75,80,84,98], thus warranting further study to fully understand its physiological role. This evidence concerns the gene UFM1 and heart disorder.