SNTA1 encodes α-1-syntrophin, a scaffold protein that is part of the dystrophin-associated protein complex. In cardiomyocytes, it interacts with SCN5A and the nNOS-PMCA4b complex. It is involved in maintaining normal cardiac function, and its mutations are associated with arrhythmia and cardiomyopathy [3].

In human cardiomyocytes with SNTA1 knocked out using the CRISPR-Cas9 system, the resulting cells exhibited a hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower calcium levels in the sarcoplasmic reticulum. Early treatment with ranolazine improved the calcium transient intensity and cardiac contractility, suggesting SNTA1-deficient cardiomyocytes can be used to research myocardial diseases and that maintaining cardiac calcium homeostasis is a key treatment target [1].

In addition, SNTA1-deficient mice lacking perivascular aquaporin-4 (AQP4) localization showed slowed cerebrospinal fluid (CSF) tracer influx, interstitial tracer efflux from the brain, and increased amyloid β levels, indicating a potential role in Alzheimer's disease development [2].

In conclusion, SNTA1 is crucial for normal cardiac function, especially in maintaining calcium homeostasis in cardiomyocytes. Its deficiency can lead to cardiac phenotypes relevant to myocardial diseases. Also, its role in perivascular AQP4 localization affects glymphatic function and amyloid β clearance, which is associated with Alzheimer's disease. Research on SNTA1-deficient models has provided valuable insights into these disease-related mechanisms.