Besides metabolic rewiring driven by oncogenic small GTPases such as KRAS, a recent study reported a reciprocal regulation of small GTPase RAC1 activity by a key metabolic enzyme LDHA through a catalytically independent mechanism.469,470 LDHA was found to bind to RAC1 and block RAC GAP access and maintain RAC1 in its active GTP bound state, leading to constitutive RAC1 activation and malignant progression and metastasis of breast cancer. The gene discussed is KRAS; the disease is breast cancer.