Articular cartilage surrounds the ends of diarthrodial joints (most common movable joints) and during motion, it experiences a wide range of loading conditions while remaining under exceedingly low-friction and wear-free conditions. This remarkable tribological performance stems from complex interactions between the synovial fluid and articular cartilage. In fact, lubricin and hyaluronic acid (HA) that are part of the synovial fluid are now known to be the key contributors to effective joint lubrication and wear protection. Studies involving animal models and artificial systems suggest that lubricin and HA molecules may work in tandem to produce a highly synergistic effect for lubrication. However, latest observations suggest that lubricin has significant potential for protecting the articular joints, probably more than HA. Recently, lurbicin-related friction regulation in soft eye tissues, where much lower forces are involved compared to knee joints for instance, has been shown to be related to dry eye disease and contact lens discomfort. As such, lubricin's role in natural friction regulation is very complex. Moreover, partially unresolved water-lubricin interactions are essential for lubrication and load carrying function in the joints. The chemical structure of lubricin has inspired several chemists to synthesize new copolymers and polymer brushes that function just like lubricin in order to design new synthetic or bio-based lubricants with ultra-low-friction coefficients. Hence, lubricin has emerged as a key natural molecule for bioinspired tribology. The aim of this review is to present the latest advances in understanding of lubricin's function in joint lubrication and in soft tissue friction (i.e., human eye) and document what has been achieved so far in transforming this biomedical knowledge into new polymer design for advanced engineering tribology. It is hoped that this review will catalyze research and development efforts in obtaining very stable and high load-bearing polymer-based ultra-low-friction surfaces via biomimicry.