After finishing her undergraduate degree, Pilane-Majake lived for ten years in the Natal Province.[2] She established her first ties to the African National Congress (ANC) during this period through her work for the South African Black Social Workers Association, an affiliate of the United Democratic Front.[3] During the political violence of the post-apartheid transition, she was a counsellor and peace broker for affected families in the region. Between 1992 and 1994, she was also a member of the National Coordination Committee for Repatriation, which oversaw the return and reintegration of South African political exiles.[3] Under the first post-apartheid government, she was the head of the South African delegation that bid for and won the right to host the 13th International Congress on Prevention of Child Abuse and Neglect, convened by the International Society for Prevention of Child Abuse and Neglect in Durban in 2000.[3]
She later returned to Tshwane to work as a consultant and project officer for the European Union Foundation for Human Rights in South Africa.[2] After that, between 2002 and 2010, she was the chief executive officer of the Commission for Gender Equality (CGE).[3] Her tenure coincided with a tumultuous period at CGE.[5][6] She was investigated – though largely cleared – by the Public Protector on maladministration charges in 2006,[7][8][9] and she was suspended from her job in April 2008 due to further complaints by staff members.[10] After a prolonged internal investigation,[11] she was summarily dismissed in March 2009, though she went on to challenge her dismissal in the High Court and also laid her own complaints with the Public Protector, including one alleging misconduct by CGE's board chairperson, Nomboniso Gasa.[12][13]
After leaving CGE in 2010, and until her election to Parliament two years later, Pilane-Majake was the executive director for human resources at VIP Consulting Engineers.[3]
However, Pilane-Majake was re-elected to her legislative seat in the election, ranked 21st on the Gauteng list,[15] and the ANC announced her appointment as programming whip in the National Assembly. In this capacity she served alongside Bheki Radebe, the house whip, and under Pemmy Majodina, the chief whip.[20] In June 2020, during a programming committee meeting about a Constitutional Court judgement that mandated amendments to the Electoral Act, she joined Majodina in complaining about judicial overreach; she said that she understood the need for judicial review of unjust laws, but that the judiciary was "more and more... just instructing Parliament" even in the absence of "a logical argument about how what is taking place is making the lives of citizens difficult".[21][22]
Pilane-Majake returned to her position as Deputy Minister of Public Service and Administration after a reshuffle by Ramaphosa on 5 August 2021. Dlodlo returned as the minister in the same reshuffle, having spent a stint as Minister of State Security.[23] She was sworn in on 6 August.[24] After her return to the ministry, Pilane-Majake represented the government at the ninth session of the Conference of the States Parties to the United Nations Convention Against Corruption in Egypt, at which she pledged the government's commitment to fighting corruption.[25]
In December 2022, she represented the Gauteng branch of the ANC at the party's 55th National Conference, where she supported Ramaphosa's successful bid to be re-elected as ANC president.[26]