Though rearrangements involving the MiT/TFE genes TFE3 and TFEB are critical drivers for a subset of PEComas, a majority of renal PEComas (including the most common and well-differentiated subtype known as angiomyolipomas) are driven by alternate genomic alterations, most commonly biallelic TSC1/2 loss resulting in mTORC1 hyperactivation. The gene discussed is TFEB; the disease is neoplasm with perivascular epithelioid cell differentiation.