Membrane occupation and recognition nexus (MORN) motif controls protein localization and function

The membrane occupation and recognition nexus (MORN) motif was first defined in 2000, when it was identified in the junctophilin protein family. Dozens of studies have been published ever since, mainly focusing on the function of a given MORN motif‐containing protein in parasites, plants or animal cells. Proteins with MORN motifs are not only expressed in most animal and plant cell types, but also significantly differ in their intracellular localization, suggesting that the MORN motifs may fulfill multiple physiological functions. Recent studies have found that MORN motif‐containing proteins junctophilin‐1/2 and MORN3 play a role in cardiac hypertrophy, skeletal muscle fiber stability and cancer. Hence, MORN motif‐containing proteins may be exploited to develop improved treatments for various pathological conditions, such as cardiovascular diseases. Here, we review current research on MORN motif‐containing proteins in different organisms and provide both ideas and approaches for follow‐up exploration of their functions and applications. Membrane occupation and recognition nexus (MORN) proteins show significant differences in localization and function among different species, which are involved in many physiological and pathological processes. We review current studies on MORN proteins and show that the differences in post‐translational modifications, amino acid side‐chain properties and spatial conformation in MORN motif and non‐MORN motif regions are important factors determining its function.