Introduction 10 25 26 1 24 26 3 7 1 7 24 37 20 29 Fig. 1 Rab REP RabGGT  blue arrows GDI  red arrows RabGEFs RabGAPs  14 32 1 Table 1 Human monogenic diseases caused by a Ras-associated binding (Rab) protein or Rab-associated protein defect Disease OMIM Gene Rab Rab-associated Description Griscelli syndrome type I 214450 MYO5A  x Autosomal recessive, albinism, neurological impairment Griscelli syndrome type II 607624 RAB27A x  Autosomal recessive, albinism, hemophagocytic syndrome, sometimes secondary neurological impairment Griscelli syndrome type III 609227 MLPH  x Autosomal recessive, albinism Choroideremia 303100 REP1  x X-linked, progressive loss of vision beginning at an early age, and the choroid and retina undergo complete atrophy Non-specific mental retardation 300104 GDI1  x X-linked, affected males show moderate to severe mental retardation, carrier females may also be mildly affected Charcot-Marie-Tooth disease type IIb 608882 RAB7 x  Autosomal dominant, peripheral sensory neuropathy with late onset muscle weakness, foot ulcers and infections Warburg Micro syndrome 600118 RAB3GAP1  x Autosomal recessive, microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy, and hypogenitalism Martsolf syndrome 212720 RAB3GAP2  x Autosomal recessive, congenital cataracts, hypogonadism, and mild mental retardation Rab proteins in skin and hear pigmentation 15 18 35 22 15 36 Rab proteins in immunology 17 33 19 19 Listeria monocytogenes 11 L. monocytogenes 6 27 Yersinia enterocolitica Salmonella typhimurium Salmonella Salmonella 23 Viruses enter host cells by receptor-mediated endocytosis, but they usually escape from endosomal vesicles to enter either the cytosol or the nucleus where they replicate. The binding of hepatitis C virus (HCV) non-structural protein (NS) with Rab1 GTPase-activating protein suggests that viruses are able to subvert host cell machinery in this way because this binding is necessary for HCV replication. 34 Rab proteins in vision 3 30 30 31 Rab proteins in neurology 9 21 38 39 39 4 5 13 4 5 Rab proteins in endocrinology 12 16 2 1 8 Rab proteins in nephrology 28 2 40 Fig. 2 AQP2 AVP V2R Gs AC O-P  American Journal of Physiology and Renal Physiology  Conclusion The Rab GTPases are a large family of proteins with a variety of regulatory functions in membrane trafficking. The central role of these proteins has become clear during the past decade, as part of the progress that has been made in understanding in detail the mechanistic principles of transport vesicle formation, movement, and fusion. Sequencing of the human genome has enabled researchers to realize the diversity of the Rab gene family, although the functions of the majority of the gene products are still unknown. The availability of complete genomic sequences as well as the important advances in molecular and cell biological methods that have already been made hold the promise of significant progress being booked in our understanding of Rab function in the near future. The identification of further genes involved not only in monogenic but also in common multifactorial human vesicle-trafficking disorders will result in a better understanding of this complex transport pathway but, more importantly, will also lead to opportunities to develop novel treatments.