CLK4 and heart failure: Pathological cardiac hypertrophy is characterized by hypertrophic growth and cardiomyocyte size increase in response to pathological stimuli.105,106 CLK4 was found to play a pivotal role in maintaining cardiac function; the deletion of CLK4 contributed to pathological myocardial hypertrophy and heart failure.56 Phosphorylation of NEXN at Ser437 by CLK4 was found to rescue pathological myocardial hypertrophy, which highlights the splicing-independent involvement of CLK4 in heart disease.