To fully apprehend the complex mechanisms responsible for intervertebral disc (IVD) degeneration, one needs to gain a deeper understanding of what characterizes a healthy disc. Using a quantitative proteomic approach, we analyzed methodically the differences existing between IVD genders, levels and components. A total of 2776 proteins were identified and we showed that cross regional but not gender variation existed along the mouse spine. Components comparison established CD109, CD81 and Col12a1 as novel NP and AF markers. NP cell clustering involved Cdh2 and tight junctions whereas early phase of adaptation to hypertonicity, the regulation of cell volume, was ensured by Slc12a2 and Wnk1. AF cells were protected from oxidative stress by expressing Atox1 and Sod3. Finally notochordal-like cells vacuoles were not acidic nor lipid droplets. Altogether, our study provides a first comprehensive landscape of the biology of a healthy murine IVD and identifies mechanisms involved in homeostasis and structure maintenance.