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Sex hormone binding globulin (SHBG) is an important protein, not only for transporting sex steroids which is its primary role, but with the discovery of a specific receptor that binds SHBG, a novel approach regarding classic ‘free-hormone hypothesis’ should be implemented. Research in SHBG gene and it expression has been done, as well as cellular signaling that controls it. It provides significant knowledge of the impact of certain well –defined cellular level signaling pathways and how they affect the level of SHBG production. Moreover, new insights have proven that SHBG isn’t just a peripherally synthesized protein. Its origin has been proven to exist in the brain, namely in the hypothalamus and the pituitary, where it is spatially closely related to oxytocin-producing neurons. The main peripheral organ that produces SHBG is the liver. Since the liver is the central metabolic organ, certain metabolic diseases will result in changed SHBG serum levels. On the other hand, endocrine disorders that affect tissues involved in sex hormone regulation will also have an impact on SHBG levels. Thusly, SHBG stands as one of the mediators between various endocrine tissues and definitely contributes with its own pathophysiological role in diseases such as: obesity, metabolic syndrome, polycystic ovary syndrome, osteoporosis, breast and prostate cancer. Its value expands to the area of clinical medicine as a marker of certain pathological states. Some studies already established its reliability and the growing trend to implement it as a useful clinical marker is present. It still remains largely understudied, from physiological and clinical aspect, but recent findings give notions that SHBG plays an important role in health and disease and could be a useful assessment marker.