SNTA1 encodes α-1-syntrophin, a scaffold protein that is part of the dystrophin-associated protein complex. It interacts with SCN5A and nNOS-PMCA4b complex in cardiomyocytes and is involved in regulating ion channels and cardiac excitability. Also, it is related to the perivascular localization of aquaporin-4 (AQP4) in the brain, thus influencing glymphatic solute transport [2,3,4,5].

In human cardiomyocytes, SNTA1-deficiency leads to a hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum, indicating its role in maintaining cardiac calcium homeostasis [1]. In a mouse model lacking perivascular AQP4 localization due to SNTA1 gene deletion, glymphatic CSF tracer influx and interstitial tracer efflux from the brain were slowed, and amyloid β levels increased, suggesting its importance in glymphatic exchange and amyloid β clearance [4].

In conclusion, SNTA1 is crucial for normal cardiac function, especially in maintaining calcium homeostasis, and also plays a role in glymphatic function in the brain. The gene knockout models of SNTA1 have provided valuable insights into its functions and its association with myocardial diseases and Alzheimer's disease-related pathology.