Slmap, the Sarcolemma Membrane Associated Protein, is a cardiac membrane protein. It plays a vital role in cardiac excitation-contraction (E-C) coupling and the heart's adrenergic response. It is also involved in the Hippo signaling pathway. In the context of heart function, its proper function is crucial for normal myocardial contraction, and its misregulation can lead to cardiac failure. Genetic models, such as KO/CKO mouse models, can be valuable in further exploring its function [1,2].

Studies show that all 3 SLMAP isoforms (SLMAP-1,-2, and-3) are expressed in cardiomyocytes (CMs) and are downregulated in human dilated ventricles. Knockdown of SLMAPs in cultured CMs mimics heart failure performance, as it reduces the spontaneous contractile rate and the response to isoproterenol. Overexpression of the SLMAP-3 isoform, however, promotes CM response to adrenergic stimuli by increasing intracellular calcium [3]. In addition, SLMAP gene polymorphisms, like rs17058639 C>T, are associated with diabetic retinopathy in the Qatari population with type 2 diabetes, suggesting its role in diabetes-related microvascular complications [4].

In conclusion, Slmap is essential for cardiac E-C coupling and the adrenergic response. Model-based research, especially through SLMAP knockdown in CMs, has revealed its role in heart failure-like phenotypes. Additionally, its genetic variants are associated with diabetes-related retinopathy, highlighting its significance in both cardiac and diabetes-related disease areas.