Other than the AR-centric underpinnings, emerging evidence has suggested that cellular plasticity, especially lineage plasticity often triggered by androgen receptor signaling inhibitors (ARSIs) such as enzalutamide (ENZ), is a key mechanism underlying CRPC development and progression, enabling PCa cells to switch from a luminal lineage to another, such as a neuroendocrine (NE) lineage, after redifferentiation, transdifferentiation, or cellular reprogramming to evade the effect of therapies (Davies et al, 2018). The gene discussed is AR; the disease is posterior cortical atrophy.