The Protein Reviews series serves as a publication vehicle for reviews that focus on crucial contemporary and vital aspects of protein structure, function, evolution and genetics. Volumes are published online first, prior to publication in a printed book. Chapters are selected according to their importance to the understanding of biological systems, relevance to the unravelling of issues associated with health and disease, or impact on scientific or technological advances and developments. Volume 21 presents eight review chapters authored by experts in the related fields. The first chapter covers the enzyme squalene monooxygenase and lipid levels and its relevance in health and disease. Chapter two presents a systematic analysis of the structural and functional aspects of heteromeric solute carriers. The third chapter provides a review of the role of CI- in type IV collagen assembly, function, and disease, including future directions for studies. This is followed by a summary in chapter four about the recent progress on defining the roles of the Slit-Robo signaling in bone metabolism and the possible roles of the interaction between Robo and neural epidermal growth factor-like proteins. Chapter five discusses recent data about the evolutionary aspects on structural differences between humans and the nematode in relation to previous knowledge of core proteins and GAG-attachment sites in Chn and CS proteoglycans of C.elegans and humans. The sixth chapter summarizes the immunochemical character of the IGHV1-69-derived RFs and the recognition mechanism of the IGHV1-69-derived RFs. Chapter seven covers regulated alternative translocation and its role as an emerging mechanism to regulate transmembrane proteins. Finally, chapter eight reviews current progress on IL-36 protein and biology and novel investigative tools. This volume is intended for research scientists, clinicians, physicians and graduate students in the fields of biochemistry, cell biology, molecular biology, immunology and genetics.