My independent career started at the University of Chile in 1999. In 2002 I moved to the P. Catholic University of Chile. My laboratory has been working in deciphering the function and intracellular trafficking of large endocytic receptors from the low-density lipoprotein receptor (LDL-R) family, including LRP1, megalin/LRP2 and ApoER2. These are multifunctional receptors of a variety of ligands with important physiological functions. Using cell lines, neurons in primary culture and animal models, my group studies the sorting signals, exocytic and endocytic pathways and the cellular machinery involved in the receptors ́trafficking as well aspects of their roles associated to neuronal function and regeneration as well to metabolic diseases (Sem Dev Biol 200)9; Biol Res 2011; Frontiers in Biol 2012; Biochem L 2017). As result of these studies, we showed for the first time the existence of apical sorting signals in the cytoplasmic domain of type one membrane protein, as is the case for Megalin. This receptor has a relevant role in the kidney and megalin reduction is associated to different diseases including Lowe Syndrome, in this case as a result of an impaired endosomal recycling (EMBO J 2011). In addition, megalin recycling is negatively regulated by phosphorylation of its tail, mediated by GSK3 (Traffic 2007). Megalin expression is positively regulated by FXR (JLR 2004) and PPAR (PLosOne 2011) and negatively by TGFβ (Ms in revision). We described that megalin is expressed in the gallbladder and could have a protective role in gallstone disease, a relevant chilean pathology (JLR 2004). On the other hand, we also described basolateral/somatodendritic sorting and recycling signals in LRP1 (Traffic 2003, MBoC 2009; Traffic 2013). LRP1 trafficking is regulated by the adaptin complex AP1B as well as by the endosomal protein SNX17 (MBoC 2009) and by Protein Kinase D (JNS 2008). Actually we are more focused in the study of ApoER2, the receptor associated to the reelin signaling pathway. ApoER2 trafficking is relevant to reelin signaling and this pathway accomplishes relevant roles in the central and peripheral nervous systems. In particular, we are interested to determine how reelin signaling impacts in membrane trafficking and cell migration as well as ApoER2 traffic is influenced by ligand-binding. We have demonstrated that ApoER2 follows a clathrin-dependent internalization (Traffic 2005) and an ARF-6 regulated endocytic pathway in the presence of its ligand (work in progress). Its endosomal recycling and signaling is regulated by SNX17 (PlosOne 2014) and ApoER2 function also includes regulation of APP-trafficking and processing (Mol Neurodeg 2007). ApoER2/reelin also regulates PNS regeneration, favoring schwann cell migration (MCN 2015) and axonal extension (Ms in preparation).