L-type Ca2+ channels (CaV1.2/1.3) convey influx of calcium ions that orchestrate a bevy of biological responses including muscle contraction, neuronal function, and gene transcription. Deficits in CaV1 function play a vital role in cardiac and neurodevelopmental disorders. Here, we develop a genetically encoded enhancer of CaV1.2/1.3 channels (GeeCL) to manipulate Ca2+ entry in distinct physiological settings. We functionalized a nanobody that targets the CaV complex by attaching a minimal effector domain from an endogenous CaV modulator-leucine-rich repeat containing protein 10 (Lrrc10). In cardiomyocytes, GeeCL selectively increased L-type current amplitude. In neurons in vitro and in vivo, GeeCL augmented excitation-transcription (E-T) coupling. In all, GeeCL represents a powerful strategy to boost CaV1.2/1.3 function and lays the groundwork to illuminate insights on neuronal and cardiac physiology and disease.