The diatom is considered one of Earth's most abundant and diverse algae groups [1]. They use chlorophyll a, c, and other pigments for photosynthesis, playing a crucial role in ocean primary production, global carbon fixation, and oxygen production [[2], [3], [4], [5]]. Diatoms thrive in various aquatic environments, adapting to diverse ecological niches and adverse temperature, salinity, and light conditions. Environments rich in nutrients, especially phosphorus (P), silica (Si), and nitrogen (N), favor their growth and proliferation due to their efficient nutrient recycling capabilities, contributing to ocean biogeochemical processes [[6], [7], [8], [9]]. Beyond their ecological role, diatoms exhibit biotechnological potential, accumulating valuable metabolites applicable to various industries. They are also known as the “green gold of the future,” being versatile and capable of thriving in different environments, with rapid growth rates and high biomass productivity [10]. Their diverse lineages provide a rich source for exploration, and their application as a biotechnological platform involves strategies to induce the accumulation of target metabolites [10,11]. Nitrogen deprivation strategy stands out for its role in enhancing bioactive compound production, which unfortunately decreases cell division rate and, therefore, biomass content [[12], [13], [14]]. This effect is evident in microalgae such as Isochrysis galbana, Nannochloropsis oceanica, Phaeodactylum tricornutum, Chlamydomonas reinhardtii, among others, which tend to accumulate neutral lipids with a substantial loss of biomass under strong nitrogen-limitation conditions. Although lipid induction is effective, the total lipid productivity may not increase due to this decline in growth (Valledor et al., 2014, Wang et al., 2019). Chaetoceros muelleri, a marine diatom native to the Northwest of Mexico, exhibits unaffected biomass under low nitrogen concentrations while inducing the accumulation of lipids and carbohydrates [17]. Unlike species such as C. reinhardtii, where nitrogen deprivation drastically affects metabolism and growth at a systemic level, involving complex networks of proteins and metabolites in the response and recovery process (Valledor et al., 2014, Goncalves et al., 2016), C. muelleri can accumulate lipids and carbohydrates without compromising its biomass. This suggests that C. muelleri possesses highly efficient intrinsic adaptive mechanisms. Understanding the molecular mechanisms involved is crucial for enhancing the economic viability of microalgae-based industries by optimizing conditions for increased high-value compound production, these industries can become more competitive. The development of genomic tools has facilitated the in-depth study of microalgae at various levels, including genomic, transcriptomic, proteomic, lipidomic, and metabolomic levels. This advancement has significantly contributed to understanding the biosynthetic pathways of valuable metabolites, identifying genes and enzymes involved, and discovering novel molecules with bioactive properties [15]. This knowledge has also paved the way for successful ventures in genetic engineering and synthetic biology, aiming to enhance the productivity of microalgal strains and harness their full potential [15,16]. Proteomics allows the identification and quantification of proteins, offering information on dynamic changes in protein expression, post-translational modifications, and protein-protein interactions. This reveals metabolic pathway remodeling, cellular process adjustments, and the activation of specific proteins or enzymes in response to stimuli [15]. The aim of this research was to analyze the proteome of the marine diatom cultivated under control conditions and two nitrogen-limiting conditions that produce high-value products (lipids and carbohydrates).