In the strive for optimal indicators of kidney damage, nephrologists may at times feel entangled in a molecular jungle. Contrary to cardiologists that succeeded in establishing highly sensitive biomarker molecules for hypoxic cellular damage, nephrologists await well-performing ‘damage’ indicators. Reasons for this are ample and mostly relate to the complex composition of the functional units along the nephrons and the diverse cellular phenotypes that may be affected by different insults (hypoxia, direct and indirect cell toxicity, autoimmunity, apoptosis and necrosis). Besides elegant studies that confirm the appropriateness of biomarkers to indicate, early and adequately, kidney damage and putatively predict outcome for kidney function, there is a need to understand the (patho-)physiological roles that these molecules play in health and disease. In this respect, a recent study by Humphreys et al. (J Clin Invest, 2013; 123: 4023) shed some light on the (patho-)physiological role that kidney injury molecule 1 (KIM-1) may play. By establishing transgenic mouse models with confined KIM-1 overexpression in proximal tubular cells, the authors are able to dissect cause and consequence, and link KIM-1 expression per se with interstitial inflammation and fibrosis. This study is remarkable for several reasons, given the profound insights into the pleiotropic functions of a single molecule, the simplicity of its design and the inclusion of adequately performed control experiment.