melanoma driver whose levels can define metastatic risk. The RAB7A gene belongs to the RAB family of genes, which is a member of the RAS oncogene family. These genes in the RAB family provides the instructions that are necessary for making proteins for vesicle trafficking. These proteins are GTPases and act like switch which is turned on and off by GTP and GDP molecules. Melanoma Melanoma cells retain a developmental memory that reflects a unique wiring of vesicles trafficking pathways. Rab7 is seen to control the proliferative and invasive potential of these aggressive tumors upon identification of melanoma enriched endolysosomal gene cluster. Lysosomal-associated degradation, a universal feature of eukaryotic cells, can be hijacked in a tumor-type- and stage –dependent manner. Finding that RAB7 is controlled by SOX10 and MYC in a MITF-independent manner has important basic and translational implications. Sox10 is not inhibited by mechanisms that downregulate MITF, some of which including BRAF mutations, are relatively frequent in malignant melanomas. This may ensure a developmental memory in the expression of RAB7. It is speculated that downregulation of RAB7 in the invasive front of aggressive melanomas is modulated by epithelial-to-mesenchymal-like mechanisms, such as those recently described to underlie the transcriptional switch associated with prometastatic phenotypes. In otherwords, there is an inherent dependency of melanoma cells on the small GTPase RAB7, identified within a lysosomal gene cluster that distinguishes this malignancy from over 35 tumor types. Analyses in human cells, clinical specimens, and mouse models demonstrated that RAB7 is an early-induced melanoma driver whose levels can be tuned to favor tumor invasion, ultimately defining metastatic risk. Importantly, RAB7 levels and function were independent of MITF and instead, the neuroectodermal master modulator SOX10 and the oncogene MYC are key RAB7a regulators. Charcot-Marie-Tooth 2B Also known as Charcot–Marie–Tooth neuropathy, hereditary motor and sensory neuropathy (HMSN) and peroneal muscular atrophy (PMA). This is a genetically and clinically heterogeneous group of inherited disorders, characterized by prominent sensory loss, often complicated by severe ulcero-mutilations of toes or feet, and variable motor involvement. Missense mutations in RAB7A, the gene encoding the small GTPase Rab7, cause CMT2B and increase Rab7 activity. Rab7 is ubiquitously expressed and is involved in degradation through the lysosomal pathway. Currently incurable, this disease is one of the most common inherited neurological disorders affecting approximately 1 in 2,500 people equating to approximately 23,000 people in the United Kingdom and 125,000 people in the United States.