Bioorthogonal ligation methods are extensively explored for the development of protein conjugates, which are of considerable importance in the therapeutic field and in biotechnology industries. Popular applications include i) the conjugation of toxins, imaging agents, or radiopharmaceuticals to monoclonal antibodies in cancer therapies, ii) the design of glycoconjugate vaccines where microbial oligosaccharides are coupled to a protein carrier, iii) the pegylation of therapeutic proteins to improve their serum half-lifes and therapeutic index. Direct protein modifications are generally performed onto amino group of the abundant lysine amino-acid with N-hydroxysuccinimide-activated esters, sulfonyl chlorides or iso(thio)cyanates. Alternatively, the relatively rare cysteine residues can also be modified for single-site functionalization through disulfide exchange and Michael addition with maleimides. In comparison, the remaining 18 amino-acid have been much less exploited. One of the most promising recent alternatives, is the click-like reactions specifically targeting the tyrosine (Y) residues. Chemical oxidation of phenyl-urazole anchors like 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD) react with phenol side chain of Y through an ene-like reaction. The method proved relatively chemoselective for Y, allowing the specific modification of peptides and proteins. Nevertheless, the method suffers from serious drawbacks such as (i) the use of an oxidizing chemical to generate the highly reactive PTAD species, (ii) the rapid PTAD decomposition in the presence of water (iii) the use of a specific buffer to scavenge the formation of an isocyanate side-product from rapid PTAD decomposition, resulting in the unwanted modification of lysines. This cross-reactivity limit the scope of the tyrosine-click reaction and the high PTAD reactivity prevents the site-specific targeting of a selected Y. The electrochemically promoted tyrosine-click-chemistry for protein labelling (e-CLICK) project will considerably broaden the scope of the click-Y by providing the reactive PTAD specie on demand, in different buffers, and without the needs of an oxidizing chemical. This ambitious goal will be reached by using a more promising strategy in terms of chemo-selectivity and protein modification. We propose here to develop the first electrochemically driven probes for Y-specific protein conjugations. The application of an appropriate electrochemical potential will allow us to activate the PTAD dormant specie in situ, on demand, without oxidizing the sensitive amino-acids from the protein or the ligands linked to the PTAD. Our preliminary results prove the feasibility on biologically relevant peptides and proteins. High coupling yields were obtained with a complete Y-selectivity and without compromising protein functionality. The possibility to activate a dormant urazole specie in situ will also offer the unique opportunity for site-specific Y electro-labeling (ss-e-click). In the currently described click-Y approaches, the most accessible Y are labeled preferentially but the distribution of the anchored urazoles at the protein surface is broad and aspecific. We strongly believe that ss-e-click will allow the selective labelling of Y residues at the entrance of protein binding sites. To reach this ambitious goal, we plan to attach the urazole anchor to a specific ligand of the targeted protein through an appropriate flexible linker. Y selectivity should be achieved after competitive binding followed by electrooxidation. We forsee that the e-CLICK and ss-e-CLICK methodology will nicely complement the arsenal of current biorthogonal ligations, allowing site-specificity in the design of covalent conjugate inhibitors, molecular probes for protein target identification, or the design of therapeutically relevant bio-conjugates.