Protein ubiquitination is a multifaceted post-translational modification that plays a crucial role in various cellular processes. Ubiquitin, a 76-amino acid protein, can be modified in multiple ways, including ubiquitination on lysine (Lys) residues or the N-terminus, leading to complex polyubiquitin chains. Additionally, ubiquitin can be modified by ubiquitin-like molecules (SUMO or NEDD8) and undergoes acetylation or phosphorylation on serine, threonine, or tyrosine residues. These modifications significantly alter signaling outcomes and have been extensively studied for their roles in different cellular processes. The review highlights recent progress in understanding the 'ubiquitin code,' which refers to the complex interplay of ubiquitin modifications. It discusses the enzymatic machinery involved in ubiquitination, including E1 activating, E2 conjugating, and E3 ligating enzymes, as well as deubiquitinating enzymes (DUBs). The review also covers the identification of specific ubiquitin modifications and their recognition by receptors containing ubiquitin-binding domains (UBDs). A significant portion of the review focuses on the emerging complexity of the ubiquitin code, particularly the roles of atypical ubiquitin chains and modifications such as SUMOylation, NEDDylation, acetylation, and phosphorylation. These modifications provide additional layers of regulation and signaling, with some modifications, like Ser65-phosphorylation, playing crucial roles in mitophagy and Parkin activation. The review concludes with a discussion on the 'ubiquitination threshold' model for proteasomal degradation, suggesting that the amount of polyubiquitin rather than the type is more critical for targeting proteins for degradation. It also emphasizes the need for new methods to study the complex architecture of branched ubiquitin chains and the potential for these chains to provide new signaling information. Overall, the review provides a comprehensive overview of the current understanding of ubiquitin modifications and their roles in cellular processes, highlighting the dynamic and multifaceted nature of the ubiquitin system.Protein ubiquitination is a multifaceted post-translational modification that plays a crucial role in various cellular processes. Ubiquitin, a 76-amino acid protein, can be modified in multiple ways, including ubiquitination on lysine (Lys) residues or the N-terminus, leading to complex polyubiquitin chains. Additionally, ubiquitin can be modified by ubiquitin-like molecules (SUMO or NEDD8) and undergoes acetylation or phosphorylation on serine, threonine, or tyrosine residues. These modifications significantly alter signaling outcomes and have been extensively studied for their roles in different cellular processes. The review highlights recent progress in understanding the 'ubiquitin code,' which refers to the complex interplay of ubiquitin modifications. It discusses the enzymatic machinery involved in ubiquitination, including E1 activating, E2 conjugating, and E3 ligating enzymes, as well as deubiquitinating enzymes (DUBs). The review also covers the identification of specific ubiquitin modifications and their recognition by receptors containing ubiquitin-binding domains (UBDs). A significant portion of the review focuses on the emerging complexity of the ubiquitin code, particularly the roles of atypical ubiquitin chains and modifications such as SUMOylation, NEDDylation, acetylation, and phosphorylation. These modifications provide additional layers of regulation and signaling, with some modifications, like Ser65-phosphorylation, playing crucial roles in mitophagy and Parkin activation. The review concludes with a discussion on the 'ubiquitination threshold' model for proteasomal degradation, suggesting that the amount of polyubiquitin rather than the type is more critical for targeting proteins for degradation. It also emphasizes the need for new methods to study the complex architecture of branched ubiquitin chains and the potential for these chains to provide new signaling information. Overall, the review provides a comprehensive overview of the current understanding of ubiquitin modifications and their roles in cellular processes, highlighting the dynamic and multifaceted nature of the ubiquitin system.